Methods for Indole Alkaloid Synthesis. A Specific Procedure for Introducing the 6,7 Double Bond into Aspidosperma-Type Alkaloids via Thiolactam Dehydrogenation

Article abstract of DOI:10.1021/ja00262a005

Tetracyclic amides 6, 14, and 19 were converted into their corresponding thiolactam derivatives 7, 15, and 20 , respectively, by treatment with Lawesson's reagent.When these thiolactams were treated with p-toluenesulfinyl chloride/i-Pr2NEt/(0 deg C) followed by aqueous workup, the α,β-unsaturated thiolactams 8, 16, and 21 were isolated in good to excellent yields.S-Alkylation of the α,β-unsaturated thiolactams followed by reduction with NaBH4 gave the tetracyclic allylic tertiary amines 10, 17, and 22.Dealkylation could only be accomplished for the N-methyl system 22, and only in modest yield.The pentacyclic amide 28 was converted into the thiolactam 29 by treatment with Lawesson's reagent, followed by p-toluenesulfinyl chloride/i-Pr2NEt/65 deg C to give the α,β-unsaturated thiolactam 30 (92percent).Extension of this exceptionally mild dehydrogenation procedure to simple monocyclic thiolactams was not successful.A mechanistic rationale for this new procedure is described with an explanation for its unusual selectivity.